Search Results (3,811)

Background: Hydromorphone is a semi-synthetic opioid agonist and a hydrogenated ketone of morphine. This study examined hydromorphone use in the United States (US) using three databases. Methods: The distribution of hydromorphone in the US (in grams) was provided by the US Drug Enforcement Administration’s Automated Reports and Consolidated Orders System (ARCOS) by state, zip code, and business type (pharmacies, hospitals, providers, etc.). Hydromorphone prescription claims were also examined using the Medicaid and Medicare Part D programs from 2010 to 2023. Results: Hydromorphone increased by +30.6% by 2013, followed by a decrease of −55.9% by 2023 in ARCOS. Medicaid prescriptions increased by +39.6% by 2015 and decreased by −48.9% by 2023. Medicare Part D claims increased by +8.5% by 2015 and decreased by −31.9% by 2023. There were also pronounced regional disparities in hydromorphone use identified in ARCOS (158.7-fold), Medicaid (17.5-fold), and Medicare Part D (13.7-fold). Conclusions: Hydromorphone use in the US has decreased substantially from 2010 to 2023. Additionally, these findings highlight considerable regional disparities, which may inform targeted opioid stewardship initiatives and guide policymakers to ensure safe and equitable opioid prescribing practices. Full article

Accurate differentiation between Coilia brachygnathus and Coilia nasus is imperative for the effective management of fisheries, the conservation of aquatic ecosystems, and the mitigation of commercial fraud. Current morphological identification remains challenging due to their high morphological similarity—particularly for processed samples—while conventional molecular methods often lack the speed or specificity required for field applications or high-throughput screening. In this study, a novel integrated approach was developed and validated, combining TaqMan quantitative real-time PCR (qPCR). for precise genotyping of C. brachygnathus and C. nasus with Recombinase Polymerase Amplification coupled with Lateral Flow Dipstick (RPA-LFD) for rapid on-site screening. First, species-specific RPA-LFD assays were designed to target the mitochondrial COI gene sequence. This enabled visual detection within 10 min at 37 °C, with a sensitivity of 10² copies/μL, and required no complex equipment. A dual TaqMan MGB qPCR assay was further developed by validating stable differentiating SNPs (chr21:3798155, C/T) between C. brachygnathus and C. nasus, using FAM/VIC dual-labeled MGB probes. Results showed that this assay could distinguish the two species in a single tube: for C. brachygnathus, Ct values in the FAM channel were significantly earlier than those in the VIC channel (ΔCt ≥ 1), with a FAM detection limit of 125 copies/reaction; for C. nasus, only VIC channel amplification was observed, with a detection limit as low as 12.5 copies/reaction. Validation with 171 known tissue samples demonstrated 100% concordance with expected species identities. This integrated approach effectively combines the high accuracy and quantitative capacity of TaqMan qPCR for confirmatory laboratory genotyping with the speed, simplicity, and portability of RPA-LFD for initial field or point-of-need screening. This reliable, efficient, and user-friendly technique provides a powerful tool for resource management, biodiversity monitoring, and ensuring the authenticity of high-quality C. brachygnathus and C. nasus. Full article

The morphological traits of Vaccinium uliginosum L., including plant height, leaf area, and fruit weight, have changed significantly across an elevational gradient in the Changbai Mountains. To elucidate the molecular mechanisms underlying these morphological variations, RNA-Seq technology was employed to identify differentially expressed genes (DEGs), key metabolic pathways, and associated biological functions of V. uliginosum at seven elevations in the Changbai Mountains. A total of 1190 DEGs significantly associated with morphological variations were identified. These genes are mainly involved in lipid synthesis, carbohydrate metabolism, energy metabolism, and signal transduction. Redundancy analysis (RDA) revealed that fatty acyl-ACP thioesterase B (FATB) and ribulose-bisphosphate carboxylase small subunit (cbbS) exhibited a significant association with morphological variation. Integrated analysis indicated that high-altitude plants likely enhance lipid synthesis and cell wall stability while also inhibiting photosynthesis and carbohydrate metabolism. The regulatory mechanisms underlying hormone signal transduction may be relatively complex, as evidenced by the enhanced activity of gibberellin and reduced biological effects of auxin, abscisic acid, and ethylene. This study is the first to provide transcriptomic evidence elucidating the genetic basis of altitudinal morphological adaptation in V. uliginosum, integrating phenotypic traits with gene expression profiles across an elevational gradient. Full article

Recent studies have indicated that territorial cohesion represents a fundamental variable for the viable functioning of a state. Territorial cohesion is the result of the interaction between two categories of forces: centripetal, which tends to maintain its cohesion, and centrifugal, which tends to break it up. These forces are the combined result of several categories of factors (ethnic, historical and geopolitical, demographic, and social–economic) which characterize each state and territory. The degree of accessibility is a composite indicator that accumulates the influence of natural and economic–social factors through the degree of development of the communications infrastructure on territorial cohesion. Accessibility is of crucial importance, especially in the case of relatively ethnically homogeneous states. Our study analyzes these aspects of territorial cohesion and administrative organization in the case of Romania, a state located in a European region of geopolitical interference and instability. By using a methodology on the critical analysis of data, documents, and bibliographic sources in Romania, the results of our study indicate changes in the relations between cities and subordinate human settlements that occurred in the last five decades, as well as the lack of financial viability of many administrative–territorial units. The conclusions of our research propose a broad rethinking of the administrative–territorial organization in this country, based mainly on better functionality and territorial cohesion. Full article

Defensins are a class of small cysteine-rich cationic antimicrobial peptides (AMPs) that play vital roles in immune-regulating insect–microbe interaction, offering great potential for developing pest control approaches using RNA interference (RNAi) and insect pathogens. However, the biocontrol potential of defensins from the destructive rice pest Nilaparvata lugens (brown planthopper, BPH) remains largely unexplored. Here, we identified and functionally characterized a defensin-encoding gene NldefB in BPH. The open reading frame (ORF) of NldefB is 315 bp in length, encoding 104 amino acids with a conserved Knot1 domain. The qRT-PCR results showed that the transcription level of NldefB went upward with the increasing developmental stages, with the highest expressions in the female adults and their fat body. The expression of NldefB was continuously induced by bacterial pathogens but exhibited a pattern of initial increase followed by a decrease when challenged by a fungal pathogen Metarhizium anisopliae. RNAi-mediated silencing of NldefB significantly decreased the host survival rate, egg production and hatchability, as well as the capability to resist fungal infection. Additionally, NldefB suppression resulted in a significant increase in microbial loads. Our findings underscored that NldefB plays essential roles in regulating host development, pathogen defense, and microbial maintenance, providing a potential target for RNAi- and microbe-mediated BPH biocontrol. Full article

Background: Metformin and proton pump inhibitors (PPIs) are independently associated with vitamin B12 deficiency. Despite frequent co-prescription, particularly in diabetics with gastroesophageal disorders, evidence regarding the combined risk of these medications on vitamin B12 deficiency remains limited. This study aimed to evaluate the real-world risk of vitamin B12 deficiency associated with metformin, PPIs, and their combinations using the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) database. Methods: We conducted a disproportionality analysis using USFDA AERS data from 2004 to 2024. We assessed whether metformin, PPIs, or their combinations were reported more often than expected with vitamin B12 deficiency and evaluated associated clinical outcomes, such as hospitalization and life-threatening events. Results: Among 29,661,136 reports, 552 met inclusion criteria, with metformin monotherapy accounting for 274 cases. Positive safety signals were detected for both metformin and all PPIs individually. While statistical interaction measures were not conclusive, patients on metformin–pantoprazole combination therapy experienced significantly higher rates of hospitalization and life-threatening events compared to those on pantoprazole alone. Conclusions: These findings suggest that patients receiving metformin and PPIs together, particularly the elderly, may face a higher risk of serious vitamin B12 deficiency-related complications. Clinicians should consider closer monitoring of vitamin B12 levels and supplementation when needed in patients on combination therapy. Full article

In Georgia (Sakartvelo), a program promoting bilingual education in preschool institutions was formally adopted in 2020. It aligns with the objectives of the 2021–2030 State Strategy for Civic Equality and Integration Plan, which envisions a comprehensive reform of bilingual education across Georgia’s regions. Any reform requires research and evaluation to measure how effectively it is being implemented and whether the intended outcomes have been achieved. The bilingual education initiative pursues a dual objective: to preserve the native languages of minority communities while ensuring effective acquisition of the state language. This dual mandate is intrinsically linked to state language policy and constitutes a sensitive issue for local communities, parents, and preschool administrators, thereby necessitating a careful and nuanced approach. The present study analyzed the readiness of the social environment to support the implementation of bilingual education programs at the preschool level in the regions of Georgia in which ethnic minorities live side by side. Research was carried out in two ethnically diverse regions—Kvemo Kartli and Samtskhe–Javakheti. The author conducted individual and group interviews, and the elicited data were analyzed with the help of content and thematic analyses. This study examines key attributes of the ongoing preschool reform to identify factors that facilitate the effective implementation of early bilingual education initiatives. The findings highlight both commonalities and regional variations in parental attitudes toward the bilingual education reform. Full article

Tree endotherapy has risen to prominence in the field of precision agriculture as an innovative and sustainable method of tree care, being respectful of both environmental protection and consumer health needs. A comprehensive review of the state of the art of research in this field has made it possible to spotlight the main advantages of tree infusion, which has undergone significant progress in step with technological innovation and an increased understanding of tree anatomy and physiology. The major criticalities associated with this technique, as well as the biological and technical–operational obstacles that still hinder its wider use, are also highlighted. What emerges is an innovative and rapidly expanding technique in tree care, in both the cultivation and phytosanitary management of fruit and ornamental trees. Some of the strengths of the endotherapy technique, such as the next-to-no water consumption, the strong reduction in the use of fertilizers and pesticides, the possibility of using biological control agents (BCAs) or other products of natural origin, the precision administration of the product inside the xylem of the tree, and the efficacy (20–90%) and persistence (1–2 years) of treatments, make it one of the cornerstones of sustainable tree protection at present. With a very low consumption of the “active ingredient”, endotherapy has a negligible impact on the external environment, minimizing the drift and dispersal of the active ingredient and thus limiting the exposure of non-target organisms such as beneficial insects, birds, and wildlife. The large-scale application of the technique would therefore also help to achieve an important goal in “climate-smart agriculture”, the saving of water resources, significantly contributing to climate change mitigation, especially in those areas of the planet where water is a precious resource. Full article

Spinal cord injury (SCI) is a devastating neurological state that could lead to motor, sensory, and autonomic dysfunction. In addition to its direct impact on the central nervous system, SCI exerts systemic effects, including disruption of gut homeostasis and alterations in the gut microbiota, which can contribute to sustained inflammation and hinder functional recovery. While antibiotic administration during the acute phase of SCI is clinically indicated, it may exacerbate microbial dysbiosis. In this study, we investigate the combined effects of SCI and cefazolin treatment on the gut microbiome of female rats. Animals were assigned to three groups: NAÏVE (no intervention), SHAM (cefazolin only), and INJURY (T10 spinal cord contusion plus cefazolin). Cefazolin was administered for seven days after the injury, fecal samples were collected at baseline (day 0), and on days 7, 14, 21, and 28 post-SCI. DNA was extracted and subjected to 16S rRNA gene amplicon sequencing, followed by bioinformatic analysis. Our findings revealed significant microbial dysbiosis in the INJURY group, including reduced alpha diversity and distinct shifts in microbial composition. These changes were most prominent during the acute phase post-SCI. Our findings highlight the compounding effects of spinal trauma and antibiotic exposure on the gut microbiome and suggest that maintaining microbial stability may represent a promising avenue to support recovery after SCI. Full article

Traditional police interrogation processes remain largely time-consuming and reliant on substantial human effort for both analysis and documentation. Intuition Artificial Intelligence (INTU-AI) is a Windows application designed to digitalize the administrative workflow associated with police interrogations, while enhancing procedural efficiency through the integration of AI-driven emotion recognition models. The system employs a multimodal approach that captures and analyzes emotional states using three primary vectors: Facial Expression Recognition (FER), Speech Emotion Recognition (SER), and Text-based Emotion Analysis (TEA). This triangulated methodology aims to identify emotional inconsistencies and detect potential suppression or concealment of affective responses by interviewees. INTU-AI serves as a decision-support tool rather than a replacement for human judgment. By automating bureaucratic tasks, it allows investigators to focus on critical aspects of the interrogation process. The system was validated in practical training sessions with inspectors and with a 12-question questionnaire. The results indicate a strong acceptance of the system in terms of its usability, existing functionalities, practical utility of the program, user experience, and open-ended qualitative responses. Full article

Two gold-decorated wooden sculptures of Qing Dynasty collected in Qianjiang Cultural Administration Institute, Chongqing, China, holds significant cultural value. Although in appearance they were preserved completely, the wooden bodies exhibited a certain degree of decay with severe peeling of the surface painted layer and gold lacquer layer. In this study, the samples from the sculptures were characterized by microscopy, SED–EDS (Scanning Electron Microscopy and Energy Dispersive Spectrometer) analysis, and Raman spectroscopy, while the preservation state of wooden core was assessed through the fluorescence microscopy and NREL (National Renewable Energy Laboratory) chemical analysis methods. Findings reveal that the raw material for wooden sculpture is cypress, and holocellulose content of wooden core is as low as 32%. The raw materials for red pigment include cinnabar (HgS) and hematite (Fe₂O₃). There are multiple layers of lacquer and gold can be observed. There is a layer made of clay, gypsum, or brick ash beneath the lacquer layer and colored layer. The gold layer on the surface adopted traditional Chinese gilding technique which is called sticking gold. This study provides insights into the material properties and technological features of these wooden sculptures, offering a reference for future protection of similar sculptures. Full article

Corporate greenwashing has emerged as a pervasive and systemic threat to global sustainability efforts, undermining regulatory effectiveness and obstructing progress toward multiple United Nations Sustainable Development Goals. As environmental opportunism increasingly diffuses across interconnected industrial supply networks, it evolves from isolated corporate misconduct into a chain-level governance challenge with significant systemic risks. Traditional governance mechanisms—whether market-based self-regulation or top-down administrative control—have proven insufficient, while the effectiveness of hybrid approaches integrating administrative coordination with market dynamics remains largely unexplored. This study investigates China’s Chain Leader Policy, a novel hybrid governance model that combines formal administrative authority with market coordination mechanisms to systematically address environmental opportunism across industrial supply networks, and its impact on mitigating greenwashing. Employing a multi-period difference-in-differences design on 12,334 firm-year observations of Chinese A-share listed companies from 2011 to 2023, we find that the policy reduces corporate greenwashing by 10.8% through four pathways: stabilizing supply–demand relationships, reducing coordination costs, fostering green collaborative innovation, and enhancing external scrutiny via social networks. Coercive isomorphism strengthens these effects, while mimetic isomorphism weakens them; impacts are more pronounced in state-owned enterprises, firms with stronger green awareness and higher levels of internationalization, and in more concentrated industries. By operationalizing embedded autonomy theory in an environmental governance context, this research extends theoretical understanding of hybrid governance mechanisms, offers robust empirical evidence for designing policies to curb greenwashing, and provides a replicable framework for achieving corporate environmental sustainability worldwide. Full article

Oyster reefs are receiving increasing attention due to severe survival challenges and their significant ecological service functions. Despite increased restorations worldwide, both natural and restored reefs have often not been monitored to an extent. Reef-building oyster populations are the foundation for the development of oyster reefs. In order to provide basic data for further protection and potential restoration of the oyster reef in the muddy tidal flats of Magu Island, in the middle of Dingzi Bay, the population structure and genetic diversity of the reef-building oysters were assessed through field investigation and molecular experiments. Results showed that the area of the oyster reef was 20,689 square meters and the oysters were Magallana gigas. The distribution of oyster patches revealed a reef building-up stage. The mean densities of the oysters were 3260.80 ind·m⁻² and 3097.60 ind·m⁻² in spring and autumn, respectively, and the biomasses were 25,209.38 g·m⁻² and 30,137.44 g·m⁻². The frequent distribution of shell height indicated two primary sizes divided by ages. Population genetic analyses based on partial mitochondrial cox1, cox3, and nad2 showed low nucleotide diversity and moderate haplotype diversity, proposing the population growth stage. Both the results of the population structure and genetic diversity suggested a developing status of the oyster reef on Magu Island. Full article

Vilobelimab, a first-in-class, human–mouse chimeric immunoglobulin G4 (IgG4) kappa monoclonal antibody, targets human complement component 5a (C5a) in plasma. Unlike upstream complement inhibitors, vilobelimab does not inhibit the generation of the membrane attack complex (C5b-9), necessary to mitigate certain infections. C5a is a strong anaphylatoxin and chemotactic agent that plays an essential role in both innate and adaptive immunity. Elevated levels of C5a have been associated with pathologic processes, including sepsis and inflammatory respiratory disorders such as acute respiratory distress syndrome (ARDS). Blocking C5a with vilobelimab has shown therapeutic promise. A randomized, multicenter placebo-controlled Phase III study of vilobelimab in patients with severe COVID-19 (PANAMO) found that patients treated with vilobelimab had a significantly lower risk of death by day 28 and 60. Based on this study, the United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Gohibic^® (vilobelimab) injection for the treatment of COVID-19 in hospitalized adults when initiated within 48 h of receiving invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). In January 2025, the European Commission (EC) granted marketing authorization for Gohibic^® (vilobelimab) for the treatment of adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ARDS who are receiving systemic corticosteroids as part of standard of care and receiving IMV with or without ECMO. Herein, we review the mechanism of action of vilobelimab in selectively inhibiting C5a-induced inflammation, outlining its bench-to-bedside development from the fundamental biology of the complement system and preclinical evidence through to the clinical data demonstrating its life-saving potential in the management of COVID-19–induced ARDS. Full article

Access to home- and community-based services (HCBSs) varies substantially between states. Yet, it is unknown how state-level policies and administrative factors impact consumer-reported unmet service needs, an important indicator of HCBS access and quality. Using the National Core Indicators—Aging and Disability Adult Consumer Survey (2016–2019; n = 13,654 community-dwelling older adults, 13 states), we examined associations between unmet HCBS needs with four state-level factors: HCBS spending relative to institutional care spending, HCBS spending per client, percentage of Medicaid beneficiaries in managed care, and Medicaid expansion; and funding program. In the adjusted logistic regression model, the odds of overall unmet HCBS needs were lower with higher percentage Medicaid beneficiaries in managed care (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.89–0.96) and Medicaid expansion (aOR, 0.80; 95% CI, 0.73–0.87) but greater with higher HCBS spending relative to institutional care spending (aOR, 1.19; 95% CI, 1.11–1.28). Compared to Medicaid waiver, odds of unmet HCBS needs were significantly lower among consumers in Managed Long-Term Services and Supports (aOR, 0.67; 95% CI, 0.61–0.74) and Program of All-Inclusive Care for the Elderly (PACE; aOR, 0.39; 95% CI, 0.31–0.49). State policies and administrative factors are important place-based determinants of HCBS consumers’ unmet HCBS needs/access; and warrant consideration in HCBS quality assurance and improvement. Full article